Mechanisms OF Chronic HBV Infection

zasxz

Mechanisms OF Chronic HBV Infection

Defective dendritic cell (DC)-T cell interaction.  A defect in T cell immunity has been assumed to be central to persistent HBV infection.  Recent studies in transgenic mice have suggested that a functional defect of DCs is an underlying cause of T cell dysfunction.  More recently, BJ Zheng and others studied monocyte-derived DCs and T cells generated from peripheral blood mononuclear cells obtained from the following groups of patients: (1) chronic HBV patients with low HBV load, (2) chronic HBV patients with high HBV load, (3) anti-HBs-positive subjects who had recovered from acute HBV infection, (4) healthy donors who had received HBV vaccination and were anti-HBs-positive, and (5) subjects who were immunologically naive to HBV exposure or vaccination.  The following DC-T cell interaction dysfunctions were observed: (1) failure of DCs to increase expression of HLA-II and B7 in response to HBsAg, (2) failure of DCs to increase IL-12 secretion in response to HBsAg, (3) defective induction of T cell proliferation in response to HBsAg, (4) failure to activate T cells to produce cytokines, and (5) defect in induction of antigen-specific cytotoxic T lymphocytes. These defects were especially prominent in patients with active HBV replication. The authors found that the functional impairment in DC-T cell interaction was improved by in vitro DC exposure to TNF-a. These data suggest that defective DC-T cell interaction may play a crucial role in the mechanism of chronic HBV infection.  Immunotherapy that reverses or improves the impaired function of DC-T cell interactions may be a potentially useful treatment for patients with chronic HBV infection.  (Zheng BJ et al. J Viral Hepat 2004;11: 217-224.)